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Type: Journal article
Title: FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex
Author: Kumar, R.
Neilsen, P.
Crawford, J.
McKirdy, R.
Lee, J.
Powell, J.
Saif, Z.
Martin, J.
Lombaerts, M.
Cornelisse, C.
Cleton-Jansen, A.
Callen, D.
Citation: Cancer Research, 2005; 65(24):11304-11313
Publisher: Amer Assoc Cancer Research
Issue Date: 2005
ISSN: 0008-5472
Statement of
Raman Kumar, Paul M. Neilsen, Joanne Crawford, Ross McKirdy, Jaclyn Lee, Jason A. Powell, Zarqa Saif, Julie M. Martin, Marc Lombaerts, Cees J. Cornelisse, Anne-Marie Cleton-Jansen, and David F. Callen
Abstract: A BAC located in the 16q24.3 breast cancer loss of heterozygosity region was previously shown to restore cellular senescence when transferred into breast tumor cell lines. We have shown that FBXO31, although located just distal to this BAC, can induce cellular senescence in the breast cancer cell line MCF-7 and is the likely candidate senescence gene. FBXO31 has properties consistent with a tumor suppressor, because ectopic expression of FBXO31 in two breast cancer cell lines inhibited colony growth on plastic and inhibited cell proliferation in the MCF-7 cell line. In addition, compared with the relative expression in normal breast, levels of FBXO31 were down-regulated in breast tumor cell lines and primary tumors. FBXO31 was cell cycle regulated in the breast cell lines MCF-10A and SKBR3 with maximal expression from late G2 to early G1 phase. Ectopic expression of FBXO31 in the breast cancer cell line MDA-MB-468 resulted in the accumulation of cells at the G1 phase of the cell cycle. FBXO31 contains an F-box domain and is associated with the proteins Skp1, Roc-1, and Cullin-1, suggesting that FBXO31 is a component of a SCF ubiquitination complex. We propose that FBXO31 functions as a tumor suppressor by generating SCFFBXO31 complexes that target particular substrates, critical for the normal execution of the cell cycle, for ubiquitination and subsequent degradation. (Cancer Res 2005; 65(24): 11304-313)
Keywords: Kidney
Tumor Cells, Cultured
Chromosomes, Artificial, Bacterial
Chromosomes, Human, Pair 16
Breast Neoplasms
Cullin Proteins
Carrier Proteins
F-Box Proteins
Cell Cycle Proteins
Tumor Suppressor Proteins
Blotting, Northern
Colony-Forming Units Assay
G1 Phase
G2 Phase
Cell Proliferation
Genes, Tumor Suppressor
Cellular Senescence
Rights: © 2005 American Association for Cancer Research
DOI: 10.1158/0008-5472.CAN-05-0936
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Paediatrics publications

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